Kidney Function and Diuretics

Role of the Kidney

• Kidneys filter toxic waste and conserve essential substances.
• Nephrons are the main structural unit.
• Diuretics act on the nephron in the glomerulus.
• GFR indicates how well the kidneys function as filters.
• GFR is regulated by afferent arterioles.
• Approximately 180L is filtered daily.
• The Proximal Convoluted Terminal returns 60-70% of sodium and water filtered back to the bloodstream.
• About 5 to 10% of sodium resorption occurs in the distal tubule.

Diuretic Drugs

• Diuretics accelerate the rate of urine formation.
• Diuretics result in the removal of sodium and water.
• Diuretics are a mainstay of therapy for hypertension, heart failure, and prevention of kidney damage during acute kidney injury.

Hypertension Canada

• The Hypertension Canada 2018 Guidelines recommend diuretics and thiazides as a first-line drug treatment option for hypertension.
• Diuretics cause direct arteriolar dilation, which decreases peripheral vascular resistance.
• These drugs reduce extracellular fluid volume, plasma volume, and cardiac output, which may account for decreased blood pressure.

Sodium and the Nephron

• In the nephron, water flows alongside sodium.
• 60 to 70% of sodium and water gets returned to the bloodstream by the proximal convoluted tubule.
• 20 to 25% of sodium is reabsorbed into the bloodstream in the ascending loop of Henle.
• 5 to 10% is reabsorbed in the distal convoluted tubule.
• The collecting duct serves as the final common pathway for the filtrate that started in the glomerulus.
• Water is excreted as urine if it is not absorbed.

Types of Diuretic Drugs

• They are classified by site of action, chemical structure, and potency.
• Loop diuretics are the most potent, followed by mannitol, metolazone, thiazide diuretics, and potassium-sparing diuretics.
• The potency of diuretics is a function of where they inhibit sodium and water resorption in the nephron.
• Diuretics have greater potency when they inhibit more sodium and water from resorption, increasing diuresis.
• The types of diuretic drugs are: Carbonic anhydrase inhibitors, loop diuretics, osmotic diuretics, potassium-sparing diuretics, and thiazide and thiazide-like diuretics.

Carbonic Anhydrase Inhibitors

• Acetazolamide is the most commonly used carbonic anhydrase inhibitor.
• It is available in oral and parenteral forms.
• Potential benefits may exceed potential fetal risks, warranting use in pregnant women.
• These medications may be used with caution in pregnant women.
• This enzyme helps make H+ ions available for exchange with sodium and water in the proximal tubules.
• Carbonic anhydrase inhibitors block the activity of carbonic anhydrase, to prevent the exchange of H+ ions with sodium and water.
• Carbonic anhydrase inhibitors reduce H+ ion concentration in renal tubules, causing increased excretion of bicarbonate, sodium, water, and potassium.
• Subsequently, there is decreased resorption of water, and urine volume is increased.
• These drugs are utilized as adjuncts in the long-term management of open-angle glaucoma and as adjunct therapy for secondary glaucoma.
• They are used with miotics to lower intraocular pressure before ocular surgery in certain cases.
• They are also useful in the treatment of edema, secondary to heart failure, high-altitude sickness, and epilepsy.
• Carbonic Anhydrase Inhibitors contraindications include known drug allergy, hyponatremia, hypokalemia, severe kidney or liver dysfunction, adrenal gland insufficiency, and cirrhosis.
• Adverse effects include acidosis, hypokalemia, drowsiness, anorexia, paresthesias, hematuria, urticaria, photosensitivity, and melena.
• When combined with digoxin, it may cause hypokalemia, increasing the risk of digoxin toxicity.

Loop Diuretics

• Examples include bumetanide, ethacrynic acid, and furosemide.
• Loop diuretics act directly on the ascending limb of the loop of Henle to block chloride and sodium resorption.
• They increase kidney prostaglandins, resulting in the dilation of blood vessels and reduced kidney, pulmonary, and systemic vascular resistance.
• They are useful in the treatment of edema.
• Loop diuretics have a quick onset and last for at least 2 hours.
• These medications cause potent diuresis and subsequent fluid loss which can reduce blood pressure, pulmonary vascular resistance, systemic vascular resistance, central venous pressure, and left ventricular end-diastolic pressure.
• This can cause potassium and sodium depletion and small calcium loss.
• These drugs are used in the treatment of edema associated with heart failure and liver or kidney disease, hypertension and to increase kidney excretion of calcium in patients with hypercalcemia.
• They are also used for heart failure resulting from diastolic dysfunction.
• Adverse effects include dizziness, headache, tinnitus, blurred vision, nausea, vomiting, diarrhea, Agranulocytosis, neutropenia, thrombocytopenia, hypokalemia, hyperglycemia, and hyperuricemia.
• Neurotoxicity and nephrotoxicity may occur with loop diuretics.
• Loop diuretics increase serum levels of uric acid, glucose, alanine aminotransferase, and aspartate aminotransferase.
• Thiazide diuretics cause sequential nephron blockade.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the reduction of vascular resistance.
• Furosemide is the most commonly used loop diuretic, used for pulmonary edema and the edema associated with heart failure, liver disease, nephrotic syndrome, ascites, and hypertension.

Osmotic Diuretics

• Mannitol is the most used osmotic diuretic.
• Other examples include urea, organic acids, and glucose.
• Osmotic diuretics function mostly in the proximal tubule and descending loop of Henle.
• These agents are nonabsorbable and create an osmotic effect.
• Osmotic diuretics pull water into the renal tubules from the surrounding tissues.
• This Inhibits tubular resorption of water and solutes, producing rapid diuresis.
• They increase glomerular filtration rate and renal plasma flow, to prevent kidney damage during acute kidney injury, and reduce intracranial pressure or cerebral edema from head trauma, and reduce excessive intraocular pressure.
• Osmotic diuretics are used in the treatment of acute kidney injury, to promote excretion of toxic substances, to reduce intracranial pressure, and to treat cerebral edema. as well as being used in the preparation of patients for transurethral surgical procedures.
• Possible adverse effects include convulsions, thrombophlebitis, pulmonary congestion, headaches, chest pains, tachycardia, blurred vision, chills, and fever.
• Mannitol is administered intravenously and may crystallize when exposed to low temperatures, therefore, vials should be stored in a warmer, and a filter should be used.

Potassium-Sparing Diuretics

• Also are known as aldosterone-inhibiting diuretics.
• Amiloride is an example.
• Spironolactone, and triamterene, or triamterene in combination with hydrochlorothiazide are potassium-sparing diuretics.
• These drugs work in collecting ducts and distal convoluted tubules, interfere with sodium-potassium exchange, competitively bind to aldosterone receptors, and block resorption of sodium and water induced by aldosterone secretion.
• They are relatively weak compared with the thiazide and loop diuretics.
• Aldosterone receptors are blocked competitively, and the action is inhibited by potassium-sparing diuretics.
• They promote the excretion of sodium and water.
• Spironolactone and triamterene are used for hyperaldosteronism, hypertension, to reverse potassium loss caused by potassium-wasting diuretics and for certain cases of heart failure.
• Amiloride is to spironolactone and triamterene but less effective in the long term.
• Potential adverse effects include dizziness, headache, cramps, nausea, vomiting, diarrhea, urinary frequency, weakness and hyperkalemia.
• Side Effects for spironolactone specifically include gynecomastia, amenorrhea, irregular menses, and postmenopausal bleeding.
• Potassium-sparing diuretics can interact with lithium, angiotensin-converting enzyme inhibitors, potassium supplements, and NSAIDS.

Thiazide and Thiazide-Like Diuretics

• Thiazide diuretics include hydrochlorothiazide.
• Thiazide-like diuretics include metolazone, chlorthalidone, and indapamide.
• These agents inhibit tubular resorption of sodium, chloride, and potassium ions in the distal convoluted tubule.
• This action results in osmotic water loss.
• Thiazide and Thiazide-Like Diuretics dilate the arterioles by direct relaxation and decrease preload and afterload.
• Thiazides should not be used if creatinine clearance is less than 30 to 50 mL/min, but metolazone remains effective to a creatinine clearance of 10 mL/min.
• Thiazide and Thiazide-Like Diuretics are indicated for hypertension, edematous states, idiopathic hypercalciuria, diabetes insipidus, and heart failure caused by diastolic dysfunction.
• Adverse effects include dizziness, headache, blurred vision, anorexia, nausea, vomiting, diarrhea, erectile dysfunction, jaundice, leukopenia, agranulocytosis, urticaria, photosensitivity, hypokalemia, glycosuria, hyperglycemia, hyperuricemia, and hypochloremic alkalosis.

Nursing Implications

• Perform a thorough patient history and physical examination.
• Assess fluid volume status, intake and output, serum electrolyte values, weight, and vital signs.
• Assess for disorders that may contraindicate cautious drug use, and instruct patients to take medication in the morning to avoid sleep interference.
• Serum potassium levels should be monitored during therapy.
• Teaching patients to maintain proper nutritional and fluid volume status is important, to maintain proper nutritional and fluid volume status.
• Patients should be taught to eat more potassium-rich foods like bananas, oranges, dates, apricots, raisins, broccoli, green beans, potatoes, tomatoes, meats, fish, wheat bread, and legumes while taking diuretics, except for potassium-sparing drugs.
• Patients taking diuretics along with digoxin should be taught to watch for digoxin toxicity.
• Patients with diabetes mellitus taking thiazide or loop diuretics should be told to monitor blood glucose for elevated levels.
• Tell the patient to change positions slowly after sitting or lying, to prevent dizziness and fainting with orthostatic hypotension, and encourage patients to keep a log of daily weight.
• Remind patients to return for follow-up visits and laboratory work.
• Patients with nausea, vomiting, or diarrhea should notify their care provider due to the possibility of fluid and electrolyte imbalances.
• Signs and symptoms of hypokalemia include anorexia, nausea, lethargy, muscle weakness, mental confusion, and hypotension.
• Patients should contact their primary care provider if they experience rapid heart rates or syncope(indicates hypotension or fluid loss).
• Excess licorice can lead to additive hypokalemia in patients taking thiazides.
• Monitor for metabolic alkalosis, drowsiness, lethargy, hypokalemia, tachycardia, hypotension, leg cramps, restlessness, and decreased mental alertness and watch for hyperkalemia in patients taking potassium sparing diuretics.
• Watch for improved edema, fluid volume overload and heart failure and therapeutic effects of hypotension and a return to normal of intraocular pressures.

Fluid Balance

• Total body water consists of: intracellular fluid (67%), interstitial fluid (25%) and plasma volume (8%).
• 60% of the adult human body is water.
• Intravascular fluid is fluid inside blood vessels, while Extravascular fluid is fluid outside of blood vessels.
• Lymph and cerebrospinal fluid are examples of extravascular fluid.
• Interstitial fluid is fluid in space between cells, tissues, and organs.
• Plasma proteins exert constant osmotic pressure.
• Colloid oncotic pressure (normally 24 mm Hg) occurs, and Interstitial fluid exerts hydrostatic pressure (normally 17 mm Hg).
• Types of fluid imbalance are edema and dehydration/fluid loss.
• Sodium is the principal extracellular electrolyte, and it plays a role in maintaining water concentration.

Crystalloids

• Solutions containing fluids and electrolytes that are normally found in the body.
• These fluids do not contain proteins (colloids).
• There is no risk for viral transmission, anaphylaxis, or alteration in coagulation profile with crystalloids.
• They are more useful for treating dehydration than for expanding plasma volume.
• Crystalloids are used as maintenance fluids to compensate for insensible fluid losses, to replace fluids, to manage specific fluid and electrolyte disturbances, and to promote urinary flow.
• Examples of crystalloids include NS (0.9% sodium chloride which is isotonic; 0.45% "half-normal" which is hypotonic), 3.3% dextrose and 0.3% NS, hypertonic saline (3% sodium chloride), lactated Ringer's solution, dextrose 5% in water, DW and 0.45% NS, and Plasma-Lyte.
• Crystalloids are indicated for Acute liver failure, Acute nephrosis, Adult respiratory distress syndrome, Burns, Cardiopulmonary bypass, Hypoproteinemia, Hemodialysis, DVT and Shock.
• Adverse effects may include edema, dilute plasma proteins, be short-lived and worsen alkalosis or acidosis.

Colloids

• Protein substances that increase colloid oncotic pressure and move fluid from the interstitial compartment to the plasma compartment when plasma protein levels are low.
• Examples are Albumin 5% and 25%, Dextran 40 or 70, and Hetastarch.
• They are usually safe.
• May cause altered coagulation resulting in bleeding and have no clotting factors or oxygen-carrying capacity.
• Rarely dextran therapy causes anaphylaxis or kidney failure.
• Albumin is a natural protein produced by the liver that generates approximately 70% of colloid oncotic pressure, and the sterile solution, prepared from pooled blood, plasma, serum, or placentas from healthy human donors, is pasteurized to destroy contaminants.

Blood Products

• They are the only class of fluids that are able to carry oxygen, and they increase tissue oxygenation and plasma volume.
• Blood products are the most expensive and least available fluid because they require human donors.
• They increase colloid osmotic pressure and plasma volume and pull fluid from extravascular space into intravascular space.
• Red blood cell products carry oxygen.
• They are derived from human donors and have the benefits and hazards of human blood.
• The indications for cryoprecipitate and plasma protein factors include management of acute bleeding (greater than 50% slow blood loss or 20% acutely), and fresh frozen plasma increases clotting factor levels in patients with demonstrated deficiency.
• Packaged red blood cells increase oxygen-carrying capacity in patients with anemia, substantial hemoglobin deficits, and those who have lost up to 25% of their total blood volume.
• Whole blood serves to increase oxygen-carrying capacity equal to packed red blood cells except that whole blood is beneficial in cases of extreme loss of blood volume because whole blood also contains plasma.
• Plasma proteins draw fluid back into blood vessels from surrounding tissues.
• Potential adverse effects include incompatibility with the recipient's immune system and transmission of pathogens.

Electrolytes

• Principal ECF electrolytes are sodium cations (Na+) and chloride anions (Cl-).
• The principal intracellular fluid electrolyte is potassium cation (K+).
• Other examples are calcium, magnesium, and phosphorus.

Potassium

• It is the most abundant positively charged electrolyte inside cells.
• 95% of body's potassium is intracellular, but the content outside of cells ranges from 3.5 to 5 mmol/L.
• Potassium levels are critical to normal body function, and it is obtained from foods like bananas, oranges, apricots, dates, raisins, broccoli, green beans, potatoes, tomatoes, meats, fish, wheat bread, and legumes.
• Excess dietary potassium is excreted via kidneys.
• Hyperkalemia is excessive serum potassium that equals a serum potassium level over 5.5 mmol/L caused by potassium supplements, angiotensin-converting enzyme inhibitors, kidney failure, excessive loss from cells, potassium-sparing diuretics, burns, trauma, metabolic acidosis, and infections.
• Hypokalemia is a deficiency of potassium, with its serum level less than 3.5 mmol/L due to excessive potassium loss from alkalosis, corticosteroids, diarrhea, ketoacidosis, hyperaldosteronism, burns, thiazide, thiazide-like, and loop diuretics, vomiting, and malabsorption.
• Hypokalemia can cause digoxin toxicity, in the presence of digoxin therapy, ventricular dysrhythmias.
• Potassium is responsible for muscle contraction, nerve impulses, regulation of heartbeat, acid-base balance, isotonicity, and electrodynamic characteristics of the cell.
• Main indication is to treat or prevent potassium depletion when dietary means are inadequate.
• Other therapeutic uses include stopping irregular heartbeats and managing tachydysrhythmias that can occur from cardiac surgery.
• Adverse effects of oral preparations are diarrhea, nausea, vomiting, and gastrointestinal bleeding and for IV administration are pain at the injection site and phlebitis.
• Excessive administration can cause with hyperkalemia, toxic effects and cardiac arrest.
• Hyperkalemia manifests in muscle weakness, paresthesia, paralysis, and cardiac rhythm irregularities, which can lead to ventricular fibrillation and cardiac arrest.
• Severe hyperkalemia is treated with IV sodium bicarbonate, calcium gluconate or calcium chloride, dextrose with insulin, and sodium polystyrene sulphonate or hemodialysis to remove excess potassium.

Sodium

• It is the most abundant positively charged electrolyte outside cells.
• The normal concentration outside cells is 135 to 145 mmol/L, maintained through a dietary intake of salt, fish, meats, and foods flavored or preserved with salt.
• Hyponatremia includes symptoms of lethargy, stomach cramps, hypotension, vomiting, and diarrhea, with causes resulting from the same conditions that cause hypokalemia, excessive perspiration, prolonged diarrhea or vomiting, kidney disorders, and adrenocortical impairment.
• Hypernatremia: symptoms include include water retention (edema), hypertension; red, flushed skin; dry, sticky mucous membranes; increased thirst; elevated temperature; decreased or absent urinary output caused by poor kidney excretion from kidney malfunction, and inadequate water consumption.
• Sodium controls water distribution, helps maintain fluid and electrolyte balance, and osmotic pressure of body fluids, and participates in acid-base balance.
• The main indication is its sodium depletion when dietary measures are inadequate (treatment or prevention), either mild needing oral sodium chloride or fluid restriction, or severe in which IV NS or lactated Ringer's is used.
• New drugs treat euvolemic hyponatremia examples which are dual arginine vasopressin V1A- and V2-receptor antagonists, and tolvaptan.
• Orally administered, effects include nausea, vomiting, and cramps, and if given intravenously, may cause venous phlebitis.

Nursing Implications

• Establish venous access as needed.
• Baseline assessments include fluid volume/electrolyte status, vital signs, skin/mucous membrane status, daily weights, and input and output.
• Assess contraindications for therapy.
• Monitor serum electrolyte levels during therapy and watch for fluid infiltration at the infusion site.
• Oral potassium needs to be diluted in water or fruit juice (100 to 250 mL) and taken with food or just after meals to minimize gastrointestinal distress and prevent rapid absorption.
• Monitor for signs of nausea, vomiting, gastrointestinal pain, and gastrointestinal bleeding.
• Colloids should be administered slowly, and fluid overload/heart failure should be observed closely.
• Transfusion reactions should be monitored closely in patients who require blood products.
• Monitor lab values, fluid status, activity tolerance and be on the lookout for adverse effects.
• Parenteral infusions of potassium must be monitored closely at at a rate of 10 mmol/hr, or 20 mmol/hr for critically ill patients with cardiac monitors, and should never be given as an IV bolus or undiluted.